2026-04-13T03:06:03Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1786412025-12-05T09:22:30Zcom_2072_1057col_2072_478799col_2072_478858col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Gómez, Antonio author Pato, Miguel L. author Bujanda, Luis author Sala Serra, Núria author Companioni Nápoles, Osmel author Cosme, Ángel author Tufano, Martina author Hanly, David J. author García, Nadia author Sanz Anquela, José Miguel author Gisbert, Javier P. author López, Consol author Elizalde, J. Ignasi author Cuatrecasas Freixas, Miriam author Andreu, Victoria author Paules, María José author Martín Arranz, María Dolores author Ortega, Luis author Poves, Elvira author Barrio, Jesús author Torres, María Ángeles author Muñoz, Guillermo author Ferrández, Ángel author Ramírez Lázaro, María José author Lario, Sergio author González, Carlos A. author Esteller, Manel author Berdasco, María author 2021-06-25T10:42:22Z 2021-06-25T10:42:22Z 2021-06-02 2021-06-25T09:44:07Z Intestinal metaplasia confers an increased risk of progression to gastric cancer. However, some intestinal metaplasia patients do not develop cancer. The development of robust molecular biomarkers to stratify patients with advanced gastric precursor lesions at risk of cancer progression will contribute to guiding programs for prevention. Starting from a genome-wide methylation study, we have simplified the detection method regarding candidate-methylation tests to improve their applicability in the clinical environment. We identified CpG methylation at the ZNF793 and RPRM promoters as a common event in intestinal metaplasia and intestinal forms of gastric cancer. Furthermore, we also showed that Helicobacter pylori infection influences DNA methylation in early precursor lesions but not in intestinal metaplasia, suggesting that therapeutic strategies to prevent epigenome reprogramming toward a cancer signature need to be adopted early in the precursor cascade. To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature. Càncer d'estómac Helicobacter pylori Stomach cancer Helicobacter pylori Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions